End-tidal carbon dioxide and amplitude spectral area as non-invasive markers of coronary perfusion pressure and arterial pressure

ABSTRACT

End-tidal carbon dioxide (ETCO 2 ) measurements may be used alone as a guide to determine when to defibrillate an individual. Alternatively, ETCO 2  measurements may be used in combination with amplitude spectral area measurements as a guide to determine when to defibrillate an individual.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to co-pending U.S. Prov. Pat. App. Ser.No. 61/829,176 filed 30 May 2013, entitled END TIDAL CARBON DIOXIDE ANDAMPLITUDE SPECTRAL AREA AS NON-INVASIVE MARKERS OF CORONARY PERFUSIONPRESSURE AND ARTERIAL PRESSURE, the entire disclosure of which is herebyincorporated by reference, for all purposes, as if fully set forthherein.

SUMMARY

Amplitude Spectrum Area (AMSA) values during ventricular fibrillation(VF) correlate with myocardial energy stores and predict defibrillationsuccess. AMSA calculations however require particular hardware and/orsoftware, and are clinically not used to determine an optimal time todeliver a defibrillation shock. By contrast, end tidal CO₂ (ETCO₂)values provide a non-invasive assessment of circulation duringcardiopulmonary resuscitation (CPR). Accordingly, it is contemplatedthat ETCO₂ measurements alone or in combination with AMSA values may beutilized as a non-invasive means to determine an optimal time to deliverdefibrillation during cardiac arrest and CPR. This is supported byacquired data that demonstrates a positive correlation between AMSA andETCO₂, as discussed throughout. In particular, it has been demonstratedthat AMSA and ETCO₂ correlate with each other and can be used tocorrelate with myocardial perfusion. This correlation may be used as away to provide additional support for more widespread use of ETCO₂ tohelp guide defibrillation therapy.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows blood flow during multiple different CPR methods (porcineVF model).

FIG. 2 shows details of a model used to demonstrate AMSA and ETCO₂correlation.

FIG. 3 shows parameter results using three different CPR techniques.

FIG. 4 shows a representative spectrum from a porcine model during eachof three methods of CPR.

FIG. 5 demonstrates a correlation between AMSA and ETCO₂.

FIG. 6 shows results of Bland-Altman analysis indicating the 95% limitsof agreement between AMSA and ETCO₂ ranged from −21.4 to −33.5.

FIG. 7 shows an example treatment system in accordance with the presentdisclosure.

FIG. 8 shows an example computing system or device.

DETAILED DESCRIPTION

Using multiple CPR methods to generate several different levels ofcoronary perfusion and cerebral perfusion, a correlation between ETCO₂and AMSA values is identified. The data establishes a firm correlationbetween ETCO₂ and AMSA, and demonstrates that ETCO₂ may be useful as anindependent indicator as to when to deliver a defibrillation shock. Inparticular, in one example embodiment, ETCO₂ measurements may be usedalone as a guide to determine when to defibrillate an individual. Inanother example embodiment, ETCO₂ measurements may be used incombination with AMSA values as a guide to determine when todefibrillate an individual. Although not so limited, an appreciation ofthe various aspects of the disclosure may be acquired from the followingdescription in connection with the drawings.

The International Consensus on Cardiopulmonary Resuscitation 2010recommends delivering a defibrillation shock every two minutes duringtreatment of cardiac arrest. The magnitude of the electrical energy ofthe delivered shock, however, has been demonstrated to be related to theseverity of post-resuscitation global myocardial dysfunction.Additionally, interruptions in precordial compressions have beendetermined to reduce coronary perfusion pressures (CoPP) which maycompromise the success of the shocks, especially after prolonged cardiacarrest. To limit the number of unnecessary shocks and interruptions inprecordial compressions, VF waveform analysis has been established topredict the success of defibrillation at any given time. Severaldifferent analysis methods have been developed and the most efficient ofthese methodologies is to examine the AMSA values. The technique todetermine AMSA values however is generally not instantaneous due to theneed to sequentially sample and filter a large amount ofelectrocardiographic data and then perform multiple calculations. Assuch, AMSA is not recommended for routine use in the guideline fordefibrillation management in adult cardiac arrest in the clinicalsetting in or out-of-hospital.

Establishing an accurate and rapid method to predict the success ofdefibrillation may have a substantial impact on the survival outcome ofa patient. Several studies have demonstrated ETCO₂ values parallelchanges in cardiac output, CoPP and myocardial perfusion while AMSAcalculations are associated with CoPP. Since both AMSA and ETCO₂ areindicated to correlate with CoPP during cardiac arrest, one aspect ofthe disclosure is that ETCO₂ would reflect AMSA values during VF and CPRbased upon the differences in flow as a consequence of the differentmethods of CPR. This association may provide a simple noninvasive meansfor medical practitioners to determine the optimal time fordefibrillation. The present disclosure demonstrates a correlationbetween the parameters of ETCO₂ and AMSA. Specifically, three CPRmethods, each generating a different level of perfusion, are utilized toestablish the association between ETCO₂ and AMSA.

For example, FIG. 1 shows blood flow during CPR in the left ventricleand brain (porcine VF model) using a standard CPR procedure (STD CPR), astandard CPR procedure using an impedance threshold device (STDCPR+ITD), and an active compression-decompression CPR procedure using animpedance threshold device (ACD CPR+ITD). As shown in FIG. 1, magnitudeof blood flow increases in order of: STD CPR (leftmost bar); STD CPR+ITD(middle bar); and ACD CPR+ITD (rightmost bar).

FIG. 2 shows detail of a swine model utilized to establish theassociation between ETCO₂ and AMSA. Twelve female farm pigs (32±1 kg)pigs (domestic crossbreed) were fasted overnight. They were sedated with10 ml (100 mg/ml) of intramuscular ketamine HCl (Ketaset, Fort DodgeAnimal Health, Fort Dodge, Iowa). An intravenous bolus of propofol(PropoFlo, Abbott Laboratories, North Chicago, Ill.) (2-3 mg/kg) wasgiven via a lateral ear vein and then infused at a rate of 160-200μg/kg/min for the remainder of the preparatory phase. The animals wereintubated with a 7.5 mm cuffed French endotracheal tube inflated toprevent air leaks. Positive pressure, volume control ventilation with atidal volume of 10 ml/kg and room air was delivered with a NarkoMed 4A(North American Drager) ventilator. The respiratory rate was adjusted(average 12±2 bpm) to keep oxygen saturation above 96% and ETCO₂ between38-42 mmHg. While in a ventral recumbent position, an intracranial boltwas inserted into the animal's parietal lobe to measure intracranialpressure using a 3.5 French micromanometer pressure transducer (Miko-TipTransducer, Millar Instruments, Inc., Houston, Tex.). The animals werethen placed supine. The left femoral artery and left external jugularvein were cannulated using a modified Seldinger percutaneous technique.Central aortic blood pressures were measured continuously via amicromanometer-tipped Millar catheter placed in the chest cavity at thelevel of origin of the thoracic descending aorta. Central venous bloodpressures were measured via a micromanometer-tipped Millar catheterplaced in the superior vena cava, approximately 2 cm above the rightatrium. Right atrial pressures were maintained between 5-7 mmHg duringthe preparatory phase. Carotid artery blood flows were measured using abidirectional Doppler flow probe attached to the internal carotid artery(Transonic Systems, Ithaca, N.Y.). Surface ECG was also monitoredcontinuously. A thermometer was placed in the rectum and bodytemperature maintained with a heating blanket between 37.0° C. and 38.0°C. during pre-study and post-ROSC phases. All data were or was digitizedusing a computer data analysis program (BIOPAC MP 150, BIOPAC SystemsInc., Calif.). ETCO₂, tidal volume, and arterial oxygen saturation wererecorded with a CO₂SMO Plus (Novametrix Medical Systems, Wallingford,Conn.).

Following preparation, the animals were positioned for CPR andpre-arrest hemodynamic variables were measured. Ventricular fibrillationwas induced in the anesthetized animal with application of a 50 Hz, 7.5V AC electrical current through an electrophysiology catheter to theendocardial surface of the right ventricle. Propofol anesthesia wasdecreased to a rate of 100 μg/kg/min and remained at this level duringCPR. After 6 minutes of untreated cardiac arrest, mechanical CPR via apneumatic piston attached to a compression pad was initiated. Chestcompressions were performed with a rate of 100/min and a depth of 25% ofthe anteroposterior diameter as previously described. All animals wereventilated during CPR with supplemental oxygen (2 LPM) with a bag-valveresuscitator at a compression to ventilation ratio of 10:1 and a tidalvolume of 10 ml/kg. As shown in FIG. 2, CPR was performed for a total of9 minutes; 3 minutes of STD CPR, 3 minutes of STD CPR+impedancethreshold device (ITD) (ResQPOD, Advanced Circulatory Systems Inc.,Roseville, Minn., USA), and 3 minutes of active compressiondecompression (ACD) CPR+ITD. The transition from one method of CPR tothe next was made in an uninterrupted manner. ACD CPR was performedusing a suction cup attached to the pneumatic piston as previouslydescribed. After the 9 minutes of CPR, epinephrine (40 μg/Kg) wasadministered intravenously and 1 minute later the pigs weredefibrillated with up to 3 additional sequential 200 Joule transthoracicbiphasic shocks. Following successful resuscitation and one hour ofobservation, the animal was given a bolus of propofol (100 mg) andeuthanized with a bolus intravenous injection of 10M KCl (30 mg/Kg).

As part of data analysis, the electrocardiographic (ECG) signal wassampled at 300 Hz and stored in 1.6 second increments such that each 4second wavelet was processed at intervals of 1.6 seconds. The ECG signalwas filtered between 3 and 30 Hz to minimize low frequency artifactsproduced by precordial compression and to exclude the electricalinterference of ambient noise at frequencies greater than 48 Hz. AnalogECG signals were digitized and converted from a time domain to afrequency domain by fast Fourier transformation via a computer dataanalysis program (BIOPAC). Utilizing MATLAB 5.1 software (MathworksInc., Natick, Mass.), the sum of individual amplitudes and frequenciesresulted in the amplitude spectrum area (i.e., AMSA). Power spectrumsfor the VF waveform were generated the same way.

The mean AMSA for each pig for each intervention was used for theanalysis. The mean values for all hemodynamic parameters extracted frommultiple 4 second intervals obtained contemporaneously with the AMSAdata were measured and used for future analysis. All values with anon-normal distribution are expressed as Median (25:75 percentiles). AFriedman statistical test was conducted to analyze ETCO₂, AMSA, thecalculated coronary and cerebral perfusion pressure, aortic systolic,diastolic and mean pressure, right atrial pressure and intracranialpressure during the three CPR methods. Coronary perfusion pressures weredetermined by the difference between the diastolic aortic pressure anddiastolic right atrial pressure during each CPR intervention. Cerebralperfusion pressures were determined by taking the difference between theaortic pressure and the intracranial pressure. Spearman correlation andFriedman tests were used to analyze the correlation between thedifferent hemodynamic parameters. A Bland and Altman assessment was usedto compare ETCO₂ and AMSA values with a range of agreement defined asmean bias±1.96 SD. P values of <0.05 were considered statisticallysignificant. Statistical analyses were performed with SPSS® Statistics17.0 (IBM Corporation, Somers, N.Y., USA).

In review of results, it was found that there were significantdifferences in the ETCO₂, AMSA, coronary perfusion pressure, cerebralperfusion pressure, systolic aortic pressure, mean aortic pressure, meanright atrial pressure and mean intracranial pressure based upon themethod of CPR used. The key perfusion parameters were lowest with STDCPR, increased with STD CPR+ITD, and were highest with ACD CPR+ITD, asshown in Table 1:

TABLE 1 ETCO2 AMSA Ao sys Ao dia Ao mean RA mean ICP mean CePP CoPP CBFSTD 5.7 31.1 30.7 9.5 20.2 12.6 18.3 2.8 8.4 25 CPR (4.5; 7.9)* (26.9;39.4)* (28.3; 35.2)* (8.4; 12.1) (18.2; 22.4)* (11.4; 15.7)* (14.8; 22)*(1.4; 8.1)* (6.1; 10)* (14; 36) STD 15.2 39.7 37.7 10.5 22.9 15.5 19.65.7 10.6 24 CPR + (13.9; 18.4) (29.9; 45.8) (33; 64.7) (8.9; 19.4) (22;39.9) (13.4; 27.5) (16.2; 23.7) (3.2; 14.8) (7.9; 13.3) (14; 29) ITD ACD20.5 45.5 41.9 11.5 25.9 16.6 18.4 7.6 13.3 27 CPR + (16.5; 21.5) (31.5;50.8) (37; 59.9) (7.6; 18) (23.7; 34.1) (14.1; 22.3) (15.2; 22.9) (4.9;17) (7.9; 19.7) (19; 45) ITD Median (25; 75 percentile); hemodynamicparameter using the three different cardiopulmonary resuscitationtechniques. Ao sys: systolic aortic pressure; Ao dia: diastolic aorticpressure; Ao mean: mean aortic pressure; RA mean: mean right atrialpressure; ICP mean: mean intracranial pressure; CePP: cerebral perfusionpressure; CoPP: Coronary perfusion pressure; ETCO₂: end tidal CO₂(mmHg); AMSA: amplitude spectral area (mV-Hz); CBF: Mean carotid bloodflow (ml/min); *p = 0.001 STD CPR < STD CPR + ITD < ACD CPR + ITD(Friedman statistical test). The data of Table 1 is shown graphically inFIG. 3, STD CPR (leftmost bar); STD CPR + ITD (middle bar); and ACDCPR + ITD (rightmost bar).

The power spectrum for the VF waveform also changed significantly basedupon the method of CPR. FIG. 4 shows a representative spectrum from onepig during each of the 3 methods of CPR, STD CPR (frontmost curve ortrend); STD CPR+ITD (middle curve or trend); and ACD CPR+ITD (rearmostcurve or trend). There was a pronounced increase in the high frequencysignal in this representative study and when the respective values forall animals were averaged.

Further analysis demonstrated a correlation between AMSA and ETCO₂(r=0.374, p=0.025) and a correlation between AMSA and key hemodynamicparameters (coronary perfusion pressure, cerebral perfusion pressure,aortic systolic, diastolic and mean pressure) (p<0.05), as shown inTable 2:

TABLE 2 Ao Ao Ao AMSA sys dia mean CePP CoPP CBF ETCO2 0.374*   0.709*  0.315    0.723*   0.526*   0.340*   0.295  0.025  <0.001    0.061 <0.001    0.001    0.043    0.08  AMSA   0.541*   0.487*   0.612*  0.217    0.185    0.639*   0.001    0.003  <0.001    0.203    0.281 <0.001  Ao   0.611*   0.953*   0.825*   0.514*   0.567* sys <0.001<0.001  <0.001    0.001  <0.001  Ao   0.709*   0.499*   0.514*   0.411*dia <0.001    0.002    0.001    0.006  Ao    0.77*   0.575*   0.597*mean <0.001  <0.001  <0.001  CePP   0.503*   0.373*   0.002  <0.001 Correlation between the different hemodynamic parameter, rs and p,*correlation is significant. Ao sys: systolic aortic pressure; Ao dia:diastolic aortic pressure; Ao mean: mean aortic pressure; RA mean: meanright atrial pressure; ICP mean: mean intracranial pressure; CePP:cerebral perfusion pressure; CoPP: Coronary perfusion pressure; ETCO₂:end tidal CO2 (mmHg); AMSA: amplitude spectral area (mV-Hz), CBF: Meancarotid blood flow (ml/min). Those are r. FIG. 5 demonstrates thecorrelation between AMSA and ETCO₂: STD CPR (diamond); STD CPR + ITD(square); and ACD CPR + ITD (triangle).

The Bland-Altman analysis indicated the 95% limits of agreement betweenAMSA and ETCO ranged from −21.4 to −33.5. This is shown graphically inFIG. 6: STD CPR (diamond); STD CPR+ITD (square); and ACD CPR+ITD(triangle). These study results indicate a strong association betweenAMSA and ETCO₂.

Research has conventionally focused on finding a non-invasive method topredict the success of defibrillation with the hope of having asubstantial impact on the survival outcome of patients. AMSA has beenreported to provide an 86% positive and an 85% negative predictivevalue, respectively for a threshold value at 21 mV×Hz. However AMSAvalues can be difficult to calculate in real-time and are notrecommended for routine use in the guideline for defibrillationmanagement in adult cardiac arrest in the clinical setting in orout-of-hospital. By contrast, continuous ETCO₂ waveforms are readilyobtainable and can be rapidly analyzed. Using three different methods ofCPR to consistently vary different organ perfusion levels, a correlationbetween ETCO₂ and AMSA is demonstrated. Because of this newly discoveredcorrelation, techniques for using ETCO₂ values, alone or in combinationwith AMSA values, to direct a caregivers are proposed as to when toapply a defibrillating shock. More specifically, if the measured ETCO₂values are within an acceptable range or near an acceptable value, anindication may be supplied to the caregiver as to when to apply adefibrillating shock.

FIG. 7 shows an example treatment system 700 in accordance with thepresent disclosure. The system 700 may include a facial mask 702 and avalve system 704. The valve system 704 may be coupled to a controller706. In turn, the controller 706 may be used to control an impedancelevel of the valve system 704. The level of impedance may be variedbased on measurements of physiological parameters, or using a programmedschedule of changes. The system 700 may include a wide variety ofsensors and/or measuring devices to measure any of a numberphysiological parameters. Such sensors or measuring devices may beintegrated within or coupled to the valve system 704, the facial mask702, etc., or may be separate depending on implementation. An example ofsensors and/or measuring devices may include a pressure transducer fortaking pressure measurements (such as intrathoracic pressures,intracranial pressures, intraocular pressures), a flow rate measuringdevice for measuring the flow rate of air into or out of the lungs, or aCO₂ sensor for measuring expired CO₂. Examples of other sensors ormeasuring devices include a heart rate sensor 708, a blood pressuresensor 710, and a temperature sensor 712. These sensors may also becoupled to the controller 706 so that measurements may be recorded.Further, it will be appreciated that other types of sensors and/ordevices may be coupled to the controller 706 and may be used toimplement defibrillation and measure various physiological parameters,such as bispectral index, oxygen saturation and/or blood levels of O₂,blood lactate, blood pH, tissue lactate, tissue pH, blood pressure,pressures within the heart, intrathoracic pressures, positive endexpiratory pressure, respiratory rate, intracranial pressures,intraocular pressures, respiratory flow, oxygen delivery, temperature,end-tidal CO₂, tissue CO₂, cardiac output, and many others.

For example, ECG electrode(s) or sensor(s) 720 may also be coupled tothe controller 706 so that measurements related to the electricalactivity of an individual's heart may be monitored and recorded.Advantageously, this may allow for the acquisition and/or derivation ofAMSA values of a particular individual during a CPR procedure, asdiscussed throughout the present disclosure. Additionally, a displayscreen 722 and one or more speakers 724 may be coupled to the controller706 to provide a prompt to a rescuer, such as a prompt to “cue” arescuer to defibrillate an individual while CPR is performed on theindividual. Such a feature is discussed in further detail in connectionwith at least FIG. 8. Even further, one or more electrodes 726 may becoupled to the controller 706 to enable application of a defibrillationshock(s) either automatically (e.g., without direct user-input) ormanually (e.g., in response to activation of a particular “button”).Still many other devices, sensors, etc., may be coupled to thecontroller 706 as needed or desired, to implement the various featuresor aspects of the present disclosure.

In some cases, the controller 706 may be used to control the valvesystem 704, to control any sensors or measuring devices, to recordmeasurements, and to perform any comparisons. Alternatively, a set ofcomputers and/or controllers may be used in combination to perform suchtasks. This equipment may have appropriate processors, display screens,input and output devices, entry devices, memory or databases, software,and the like needed to operate the system 700. A variety of devices mayalso be coupled to controller to cause the person to artificiallyinspire. For example, such devices may comprise a ventilator 714, aniron lung cuirass device 716 or a phrenic nerve stimulator 718. Theventilator 714 may be configured to create a negative intrathoracicpressure within the person, or may be a high frequency ventilatorcapable of generating oscillations at about 200 to about 2000 perminute. Other embodiments are possible.

FIG. 8 shows an example computer system or device 800 in accordance withthe present disclosure. An example of a computer system or deviceincludes a medical device, a desktop computer, a laptop computer, atablet computer, and/or any other type of machine configured forperforming calculations. The example computer device 800 may beconfigured to perform and/or include instructions that, when executed,cause the computer system 800 to perform a method for providing a guideto determine when to defibrillate an individual using ETCO₂ measurementsalone. The example computer device 800 may be configured to performand/or include instructions that, when executed, cause the computersystem 800 to perform a method for providing a guide to determine whento defibrillate an individual using ETCO₂ measurements and AMSA values.The particular trigger of when to provide the shock may be based on parton the correlation between the ETCO₂ measurements and predetermined AMSAvalues, or may be determined empirically based on test data using ETCO₂measurements. It is thus contemplated that the example computer device800 may be coupled to one or more sensors configured and arranged toacquire and/or operate on such measurements or data, itself haveintegrated therein one or more sensors configured and arranged toacquire and/or operate on such measurements or data, or any combinationthereof.

Furthermore, it is contemplated that the example computer system 800 mayinclude or comprise at least one of an audio speaker and a displaymonitor so as to provide at least one of an audio indication (e.g., aparticular tone or series of tones such as a single or periodic orintermittent “beep,” a particular word such as a “go” or “defibrillate,”and etc.) and a visual indication (e.g., a particular colored screen orseries of screens such as a “green” screen or periodically orintermittently “flashing” screens of one or more particular colors, aparticular graphic such as a “go” or “defibrillate,” and etc.) so that amedical professional or other individual may be “cued” to defibrillatean individual during CPR as performed on the individual as discussedthroughout the present disclosure. Such features may be embodied by theoutput device(s) 808 shown in FIG. 8 discussed further below.

The computer device 800 is shown comprising hardware elements that maybe electrically coupled via a bus 802 (or may otherwise be incommunication, as appropriate). The hardware elements may include aprocessing unit with one or more processors 804, including withoutlimitation one or more general-purpose processors and/or one or morespecial-purpose processors (such as digital signal processing chips,graphics acceleration processors, and/or the like); one or more inputdevices 806, which may include without limitation a remote control, amouse, a keyboard, and/or the like; and one or more output devices 808,which may include without limitation, a video monitor or screen, anaudio speaker, a printer, and/or the like.

The computer system 800 may further include (and/or be in communicationwith) one or more non-transitory storage devices 810, which maycomprise, without limitation, local and/or network accessible storage,and/or may include, without limitation, a disk drive, a drive array, anoptical storage device, a solid-state storage device, such as a randomaccess memory, and/or a read-only memory, which may be programmable,flash-updateable, and/or the like. Such storage devices may beconfigured to implement any appropriate data stores, including withoutlimitation, various file systems, database structures, and/or the like.

The computer device 800 might also include a communications subsystem812, which may include without limitation a modem, a network card(wireless or wired), an infrared communication device, a wirelesscommunication device, and/or a chipset, such as a Bluetooth™ device, an802.11 device, a WiFi device, a WiMax device, hardwired and/or wirelesscommunication facilities, and/or the like. The communications subsystem812 may permit data to be exchanged with a private and/or non-privatenetwork, other computer systems, and/or any other devices describedherein. In many embodiments, the computer system 800 may furthercomprise a working memory 814, which may include a random access memoryand/or a read-only memory device, as described above.

The computer device 800 also may comprise software elements, shown asbeing currently located within the working memory 814, including anoperating system 816, device drivers, executable libraries, and/or othercode, such as one or more application programs 818, which may comprisecomputer programs provided by various embodiments, and/or may bedesigned to implement methods, and/or configure systems, provided byother embodiments, as described herein. By way of example, one or moreprocedures described with respect to the method(s) discussed above,and/or system components might be implemented as code and/orinstructions executable by a computer (and/or a processor within acomputer); in an aspect, then, such code and/or instructions may be usedto configure and/or adapt a general purpose computer (or other device)to perform one or more operations in accordance with the describedmethods.

A set of these instructions and/or code might be stored on anon-transitory computer-readable storage medium, such as the storagedevice(s) 810 described above. In some cases, the storage medium mightbe incorporated within a computer system, such as computer system 800.In other embodiments, the storage medium might be separate from acomputer system (e.g., a removable medium, such as flash memory), and/orprovided in an installation package, such that the storage medium may beused to program, configure, and/or adapt a general purpose computer withthe instructions/code stored thereon. These instructions might take theform of executable code, which is executable by the computer device 800and/or might take the form of source and/or installable code, which,upon compilation and/or installation on the computer system 800 (e.g.,using any of a variety of generally available compilers, installationprograms, compression/decompression utilities, etc.), then takes theform of executable code.

It will be apparent to those skilled in the art that substantialvariations may be made in accordance with specific requirements. Forexample, customized hardware might also be used, and/or particularelements might be implemented in hardware, software (including portablesoftware, such as applets, etc.), or both. Further, connection to othercomputing devices such as network input/output devices may be employed.

As mentioned above, in one aspect, some embodiments may employ acomputer system (such as the computer device 800) to perform methods inaccordance with various embodiments of the invention. According to a setof embodiments, some or all of the procedures of such methods areperformed by the computer system 800 in response to processor 804executing one or more sequences of one or more instructions (which mightbe incorporated into the operating system 816 and/or other code, such asan application program 818) contained in the working memory 814. Suchinstructions may be read into the working memory 814 from anothercomputer-readable medium, such as one or more of the storage device(s)810. Merely by way of example, execution of the sequences ofinstructions contained in the working memory 814 may cause theprocessor(s) 804 to perform one or more procedures of the methodsdescribed herein.

The terms “machine-readable medium” and “computer-readable medium,” asused herein, may refer to any medium that participates in providing datathat causes a machine to operate in a specific fashion. In an embodimentimplemented using the computer device 800, various computer-readablemedia might be involved in providing instructions/code to processor(s)804 for execution and/or might be used to store and/or carry suchinstructions/code. In many implementations, a computer-readable mediumis a physical and/or tangible storage medium. Such a medium may take theform of a non-volatile media or volatile media. Non-volatile media mayinclude, for example, optical and/or magnetic disks, such as the storagedevice(s) 810. Volatile media may include, without limitation, dynamicmemory, such as the working memory 814.

Example forms of physical and/or tangible computer-readable media mayinclude a floppy disk, a flexible disk, hard disk, magnetic tape, or anyother magnetic medium, a CD-ROM, any other optical medium, a RAM, aPROM, EPROM, a FLASH-EPROM, any other memory chip or cartridge, or anyother medium from which a computer may read instructions and/or code.

Various forms of computer-readable media may be involved in carrying oneor more sequences of one or more instructions to the processor(s) 804for execution. By way of example, the instructions may initially becarried on a magnetic disk and/or optical disc of a remote computer. Aremote computer might load the instructions into its dynamic memory andsend the instructions as signals over a transmission medium to bereceived and/or executed by the computer system 800.

The communications subsystem 812 (and/or components thereof) generallywill receive signals, and the bus 802 then might carry the signals(and/or the data, instructions, etc. carried by the signals) to theworking memory 814, from which the processor(s) 804 retrieves andexecutes the instructions. The instructions received by the workingmemory 814 may optionally be stored on a non-transitory storage device810 either before or after execution by the processor(s) 804.

As may be understood from the foregoing discussion in connection withthe drawings, it is contemplated that ETCO₂ measurements may be usedalone as a guide to determine when to defibrillate an individual.Alternatively, ETCO₂ measurements may be used in combination withamplitude spectral area measurements as a guide to determine when todefibrillate an individual.

In particular, in some aspects, a computer-implemented method mayinclude or comprise obtaining, by a computing or measuring system, anETCO₂ measurement of an individual during a CPR procedure performed onthe individual. The method may further include or comprise comparing, bythe computing system, a particular ETCO₂ value derived from the ETCO₂measurement to a predetermined threshold value. The method may furtherinclude or comprise providing, by the computing system based on thecomparing, a perceivable indication that designates a time to deliver adefibrillation shock to the individual. Further, the computing systemmay, in some embodiments, use a change from one time point to the nextor another, in ETCO₂ measurements, to determine the time to delivery ofa defibrillation shock. The ETCO₂ measurements could include peak and/ortrough ETCO₂ values, mean values, or ETCO₂ waveform characteristicswhich are affected by the amount of blood circulating or in circulationduring CPR in the individual.

Additionally, or alternatively, the method may include or compriseproviding the indication when the particular ETCO₂ value is less than orequal to the predetermined threshold value. For example, when ETCO₂levels are persistently less than 10 mmHg, then the chances for asuccessful defibrillation may be considered to be extremely low and suchinformation may be used by the computing system to determine that adefibrillatory shock should not be delivered at that time. Additionally,or alternatively, the method may include or comprise providing theindication when the particular ETCO₂ value is greater than or equal tothe predetermined threshold value.

Additionally, or alternatively, the method may include or compriseproviding, by the computing system based on the comparison, at least oneof an audio indication and a visual indication that designates the timeto deliver the defibrillation shock to the individual. The visualindication could be provided in the form of an absolute number or agraph of changes in ETCO₂ or a derivative of ETCO₂ over time, with anindication for the threshold value needed before a shock should bedelivered.

Additionally, or alternatively, the method may include or compriseobtaining an electrocardiogram (ECG) measurement of the individualduring the CPR procedure; deriving from the ECG measurement an amplitudespectral area value; and providing the indication that designates thetime to deliver the defibrillation shock to the individual based uponthe amplitude spectrum area value and the comparison of the ETCO₂ valueto the predetermined threshold value. For example, both AMSA and ETCO₂values would have to be at a threshold value before a shock isdelivered, thereby providing the greatest likelihood for a successfuldefibrillation and survival. In this manner, the computing system maytake into account both measurements before advising or triggering adefibrillatory shock. Other potential combinations of these twodistinctly different physiological signals to provide a greater degreeof predictive certainty of defibrillation success or failure include thevalue obtained by multiplying, or performing another mathematicaloperation, the ETCO₂ and AMSA values together to achieve a number thatwould provide an indicator that defibrillation would be successful.

In some aspects, a method may include or comprise performing acardiopulmonary resuscitation (CPR) procedure on an individual; anddelivering a defibrillation shock to the individual at a particular timebased upon an indication provided by a computing system when aparticular end-tidal carbon dioxide (ETCO₂) value derived from an ETCO₂measurement of the individual during the CPR procedure is determined bythe computing system as less than or greater than a predeterminedthreshold value. In some embodiments, once the rescuer observes theindication, then they would deliver the defibrillatory shock within thenext 30-60 seconds. In cases where the shock is not successful, afollow-up ETCO₂ value could be used to determine if an additional 1-2minutes of CPR is needed or whether the rescuer should charge thedefibrillator and immediately deliver another shock. Thus, the postshock ETCO₂ value could be used to help determine the timing of followup shocks if the first one is not successful. The computing system mayadjust for the failed shock such that the next shock would not beadvised unless the ETCO₂ values were higher, for example, 10% higherthan those measured prior to the first shock.

Additionally, or alternatively, the method may include or compriseperforming an intrathoracic pressure regulation procedure or areperfusion injury protection procedure at or during the CPR procedure.Additionally, or alternatively, the method may include or compriseperiodically extracting respiratory gases from the airway of theindividual to create an intrathoracic vacuum that lowers pressure in thethorax to at least one of: enhance the flow of blood to the heart of theindividual; lower intracranial pressures of the individual; and enhancecerebral profusion pressures of the individual. Additionally, oralternatively, the method may include or comprise preventing air from atleast temporarily entering the lungs of the individual during at least aportion of a relaxation or decompression phase of the CPR procedure tocreate an intrathoracic vacuum that lowers pressure in the thorax to atleast one of: enhance flow of blood to the heart of the particularindividual; lower intracranial pressures of the particular individual;and enhance cerebral profusion pressures of the individual. The methodsand devices used to perform CPR could include manual closed chest CPR,CPR with an active compression decompression device, and such CPRmethods could be used together with an impedance threshold device totransiently impede inspiratory flow during the recoil phase of CPR or anintrathoracic pressure regulatory to actively extract gases form thelungs.

Additionally, or alternatively, the method may include or compriseperforming a standard CPR procedure on the individual. Additionally, oralternatively, the method may include or comprise performing a stutterCPR procedure on the individual to achieve some degree of reperfusioninjury protection. Additionally, or alternatively, the method mayinclude or comprise performing an active compression-decompression CPRprocedure on the individual. Additionally, or alternatively, the methodmay include or comprise positioning a mechanical CPR device relative tothe chest of the individual; and activating the mechanical CPR device toperform a mechanized CPR procedure on the individual. Such CPR devicescould include, but would not be limited to, a LUCAS device(Physio-control, Redmond, Wash.). The Zoll Autopulse (Chelmsford,Mass.), the Michigan Instrument Thumper (Grand Rapids, Mich.).

Additionally, or alternatively, the method may include or comprisedelivering the defibrillation shock to the individual upon perception ofthe indication provided by the computing system at the particular timebased upon an amplitude spectrum area value of the individual as derivedfrom a measurement during the CPR procedure and when the particularETCO₂ value is determined as less than or equal, or greater than orequal to the predetermined threshold value. Additionally, oralternatively, the method may include or comprise delivering thedefibrillation shock to the individual upon perception of at least oneof an audio indication and a visual indication provided by the computingsystem.

In some aspects, a system, device, or apparatus may include or comprisea first device that monitors concentration of carbon dioxide inrespiratory gases of an individual at least during a cardiopulmonaryresuscitation (CPR) procedure performed on the individual; a seconddevice that compares a particular end-tidal carbon dioxide value derivedfrom the concentration of carbon dioxide in respiratory gases of theindividual to a predetermined threshold value; and a third device thatprovides based on the comparison a perceivable indication thatdesignates a time to deliver a defibrillation shock to the individual.The second device may be used with the third device to determine theoptimal time to deliver the shock and, if the first shock fails, may usethe same or different logic to determine the time to deliver additionalshocks.

Additionally, or alternatively, the system, device, or apparatus mayinclude or comprise an electroencephalogram (EEG) sensor that measuresan EEG signal of the individual at least during the CPR procedureperformed on the individual, wherein the second device derives anamplitude spectrum area value from the EEG signal, and the third deviceprovides the perceivable indication based upon the amplitude spectrumarea value and the comparison of the particular end-tidal carbon dioxidevalue to the predetermined threshold value. Additionally, oralternatively, the system, device, or apparatus may include or comprisea circulation enhancement device that enhances circulation of theindividual at least during the CPR procedure performed on theindividual.

The methods, systems, and devices discussed above are examples. Variousconfigurations may omit, substitute, or add various method steps orprocedures, or system components as appropriate. For instance, inalternative configurations, the methods may be performed in an orderdifferent from that described, and/or various stages may be added,omitted, and/or combined. Also, features described with respect tocertain configurations may be combined in various other configurations.Different aspects and elements of the configurations may be combined ina similar manner. Also, technology evolves and, thus, many of theelements are examples and do not limit the scope of the disclosure orclaims.

Specific details are given in the description to provide a thoroughunderstanding of example configurations (including implementations).However, configurations may be practiced without these specific details.For example, well-known circuits, processes, algorithms, structures, andtechniques have been shown without unnecessary detail in order to avoidobscuring the configurations. This description provides exampleconfigurations only, and does not limit the scope, applicability, orconfigurations of the claims. Rather, the preceding description of theconfigurations will provide those skilled in the art with an enablingdescription for implementing described techniques. Various changes maybe made in the function and arrangement of elements without departingfrom the spirit or scope of the disclosure.

Also, configurations may be described as a process which is depicted asa flow diagram or block diagram. Although each may describe theoperations as a sequential process, many of the operations may beperformed in parallel or concurrently. In addition, the order of theoperations may be rearranged. A process may have additional steps notincluded in the figure. Furthermore, examples of the methods may beimplemented by hardware, software, firmware, middleware, microcode,hardware description languages, or any combination thereof. Whenimplemented in software, firmware, middleware, or microcode, the programcode or code segments to perform the necessary tasks may be stored in anon-transitory computer-readable medium such as a storage medium.Processors may perform the described tasks.

Furthermore, the example embodiments described herein may be implementedas logical operations in a computing device in a networked computingsystem environment. The logical operations may be implemented as: (i) asequence of computer implemented instructions, steps, or program modulesrunning on a computing device; and (ii) interconnected logic or hardwaremodules running within a computing device.

Although the subject matter has been described in language specific tostructural features and/or methodological acts, it is to be understoodthat the subject matter defined in the appended claims is notnecessarily limited to the specific features or acts described above.Rather, the specific features and acts described above are disclosed asexample forms of implementing the claims.

What is claimed is:
 1. A computer-implemented method, comprising:obtaining, by a computing system, an end-tidal carbon dioxide (ETCO₂)measurement of an individual during a cardiopulmonary resuscitation(CPR) procedure performed on the individual; comparing, by the computingsystem, a particular ETCO₂ value derived from the ETCO₂ measurement to apredetermined threshold value; and providing, by the computing systembased on the comparing, a perceivable indication that designates a timeto deliver a defibrillation shock to the individual.
 2. The method ofclaim 1, further comprising: providing the indication when theparticular ETCO₂ value is less than or equal to the predeterminedthreshold value.
 3. The method of claim 1, further comprising providingthe indication when the particular ETCO₂ value is greater than or equalto the predetermined threshold value.
 4. The method of claim 1, furthercomprising: providing, by the computing system based on the comparison,at least one of an audio indication and a visual indication thatdesignates the time to deliver the defibrillation shock to theindividual.
 5. The method of claim 1, further comprising: obtaining anelectrocardiogram (ECG) measurement of the individual during the CPRprocedure; deriving from the ECG measurement an amplitude spectral areavalue; and providing the indication that designates the time to deliverthe defibrillation shock to the individual based upon the amplitudespectrum area value and the comparison of the ETCO₂ value to thepredetermined threshold value.
 6. A method, comprising: performing acardiopulmonary resuscitation (CPR) procedure on an individual; anddelivering a defibrillation shock to the individual at a particular timebased upon an indication provided by a computing system when aparticular end-tidal carbon dioxide (ETCO₂) value derived from an ETCO₂measurement of the individual during the CPR procedure is determined bythe computing system as less than or greater than a predeterminedthreshold value.
 7. The method of claim 6, further comprising:performing an intrathoracic pressure regulation procedure or areperfusion injury protection procedure at or during the CPR procedure.8. The method of claim 6, further comprising: periodically extractingrespiratory gases from the airway of the individual to create anintrathoracic vacuum that lowers pressure in the thorax to at least oneof: enhance the flow of blood to the heart of the individual; lowerintracranial pressures of the individual; and enhance cerebral profusionpressures of the individual.
 9. The method of claim 6, furthercomprising: preventing air from at least temporarily entering the lungsof the individual during at least a portion of a relaxation ordecompression phase of the CPR procedure to create an intrathoracicvacuum that lowers pressure in the thorax to at least one of: enhanceflow of blood to the heart of the particular individual; lowerintracranial pressures of the particular individual; and enhancecerebral profusion pressures of the individual.
 10. The method of claim6, further comprising performing a standard CPR procedure on theindividual.
 11. The method of claim 6, further comprising performing astutter CPR procedure on the individual.
 12. The method of claim 6,further comprising performing an active compression-decompression CPRprocedure on the individual.
 13. The method of claim 6, furthercomprising: positioning a mechanical CPR device relative to the chest ofthe individual; and activating the mechanical CPR device to perform amechanized CPR procedure on the individual.
 14. The method of claim 6,further comprising: delivering the defibrillation shock to theindividual upon perception of the indication provided by the computingsystem at the particular time based upon an amplitude spectrum areavalue of the individual as derived from a measurement during the CPRprocedure and when the particular ETCO₂ value is determined as less thanor equal to the predetermined threshold value.
 15. The method of claim6, further comprising: delivering the defibrillation shock to theindividual upon perception of the indication provided by the computingsystem at the particular time based upon an amplitude spectrum areavalue of the individual as derived from a measurement during the CPRprocedure and when the particular ETCO₂ value is determined as greaterthan or equal to the predetermined threshold value.
 16. The method ofclaim 6, further comprising: delivering the defibrillation shock to theindividual upon perception of at least one of an audio indication and avisual indication provided by the computing system.
 17. An apparatus,comprising: a first device that monitors concentration of carbon dioxidein respiratory gases of an individual at least during a cardiopulmonaryresuscitation (CPR) procedure performed on the individual; a seconddevice that compares a particular end-tidal carbon dioxide value derivedfrom the concentration of carbon dioxide in respiratory gases of theindividual to a predetermined threshold value; and a third device thatprovides based on the comparison a perceivable indication thatdesignates a time to deliver a defibrillation shock to the individual.18. The apparatus of claim 17, further comprising: anelectroencephalogram (EEG) sensor that measures an EEG signal of theindividual at least during the CPR procedure performed on theindividual, wherein the second device derives an amplitude spectrum areavalue from the EEG signal, and the third device provides the perceivableindication based upon the amplitude spectrum area value and thecomparison of the particular end-tidal carbon dioxide value to thepredetermined threshold value.
 19. The apparatus of claim 17, furthercomprising: a circulation enhancement device that enhances circulationof the individual at least during the CPR procedure performed on theindividual
 20. The apparatus of claim 17, wherein the third device isselected from one of a visual output device and an audio output device.